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Patent 2666033 Summary

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(12) Patent Application: (11) CA 2666033
(54) English Title: IMPROVED COOLER/HEATER ARRANGEMENT
(54) French Title: APPAREIL AMELIORE DE REFROIDISSEMENT OU DE CHAUFFAGE
Status: Deemed Abandoned and Beyond the Period of Reinstatement - Pending Response to Notice of Disregarded Communication
Bibliographic Data
(51) International Patent Classification (IPC):
  • C12M 1/38 (2006.01)
  • B01L 7/00 (2006.01)
  • C09K 5/14 (2006.01)
  • C12P 19/34 (2006.01)
  • F28F 3/02 (2006.01)
(72) Inventors :
  • HARTTIG, HERBERT (Germany)
(73) Owners :
  • F. HOFFMANN-LA ROCHE AG
(71) Applicants :
  • F. HOFFMANN-LA ROCHE AG (Switzerland)
(74) Agent: BORDEN LADNER GERVAIS LLP
(74) Associate agent:
(45) Issued:
(22) Filed Date: 2009-05-15
(41) Open to Public Inspection: 2009-11-19
Availability of licence: N/A
Dedicated to the Public: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): No

(30) Application Priority Data:
Application No. Country/Territory Date
08104005.7 (European Patent Office (EPO)) 2008-05-19

Abstracts

English Abstract


Subject of the present invention is a device for heating and cooling an object
in a controlled
manner permitting a good thermal contact between the thermal block, the
element for
heating and cooling and the heat sink without the need for using a thermal
interface
material, an instrument comprising such a device and a method for conducting a
thermal
profile using the device.


Claims

Note: Claims are shown in the official language in which they were submitted.


19
CLAIMS
1. A device for heating and cooling an object in a controlled manner, said
device
comprising layered on top of another in the following order from top to bottom
- a thermal block (1),
- an element for heating and cooling (4), and
- a heat sink (5),
characterized in that the surface of the thermal block facing the element for
heating
and cooling (1a) and / or the surface of the element for heating and cooling
facing the
thermal block (4a) is covered with a solid film lubricant.
2. The device for heating and cooling according to claim 1, wherein in
addition the
surface of the element for heating and cooling facing the heat sink (4b) and /
or the
surface of the heat sink facing the element for heating and cooling (5a) is
covered with
a solid film lubricant.
3. The device for heating and cooling according to any one of claims 1 or 2,
wherein said
solid film lubricant is selected from the group of homogeneous films
containing poly-
tetrafluoroethene or poly-tetrafluoroethylene (PTFE), polyimide, parylene F,
fluorinated ethylene propylene (FEP) or other fluor containing polymers or any
mixture thereof, microcrystalline diamond or diamond like carbon (DLC),
heterogeneous films comprising an organic matrix with organic or inorganic
lubricant
particles.
4. The device for heating and cooling according to any one of claims 1 to 3,
wherein two
surfaces facing each other are coated with different solid film lubricants.
5. The device for heating and cooling according to any one of claims 1 to 4,
wherein two
surfaces facing each other are coated with identical solid film lubricants.
6. An instrument for performing thermal cycles at least comprising a device
for heating
and cooling according to any one of claims 1 to 5.

20
7. An instrument according to claim 6, wherein said device is positioned
within the
instrument in such a manner to permit a defined and predetermined physical
interaction with a receptacle, when said receptacle is inserted into the
instrument and
brought into contact with said device.
8. An instrument according to any one of claims 6 and 7 further comprising a
heat
control.
9. A method for conducting a thermal profile comprising
- providing a receptacle on a thermal block of a device for heating and
cooling
according to any one of claims 1 to 5,
- providing a fluid to be heated and / or cooled in said receptacle,
- applying heat or cold to said fluid in said receptacle using said element
for
heating and cooling.
10. The method according to claim 9, wherein said thermal profile contains
repeated
thermocycles.
11. The method according to any one of claims 9 or 10, wherein the thermal
profile is
suitable for performing a polymerase chain reaction and the fluid to be heated
is a
reaction mixture for performing a polymerase chain reaction containing a
nucleic
acid sample to be amplified.

Description

Note: Descriptions are shown in the official language in which they were submitted.


CA 02666033 2009-05-15
Improved cooler / heater arrangement
Field of the invention
Subject of the present invention is a device for heating and cooling an object
in a controlled
manner, an instrument for performing thermal cycles, and a method for
conducting a
thermal profile.
Background of the invention
The invention is particularly useful in the field of health care as well as
research in biological
and medical science, particularly in nucleic acid analysis, gene
quantification and
genotyping, where reliable analysis of samples for components contained
therein is needed.
Methods and devices for amplifying nucleic acids are well known in the art.
A method that uses reactions cycles including denaturation and amplification
steps is the
polymerase chain reaction (PCR). This technology has revolutionized the field
of nucleic
acid treatment, particularly the analysis of nucleic acids, by providing a
tool to increase the
amount of nucleic acids of a particular sequence from negligible to detectable
amounts.
PCR is described e.g. in EP 0 201 184 and EP 0 200 362. More recently improved
and more
powerful PCR techniques have been developed. Quantitative real time PCR is a
laboratory
technique used to simultaneously amplify and quantify a specific part of a
given DNA
molecule. It is used to determine whether or not a specific sequence is
present in the sample
and if present, the number of copies in the sample can be quantified. Two
common
methods of quantification are the use of fluorescent dyes that intercalate
with double-strand
DNA and modified DNA oligonucleotide probes that fluoresce when hybridized
with a
complementary DNA. Such methods are described e.g. in EP 0 512 334.
Furthermore, multiplex PCR was developed that enables amplification of two or
more
products in parallel in a single reaction tube. It is widely used in
genotyping applications
and different areas of DNA testing in research, forensic, and diagnostic
laboratories.
Multiplex PCR can also be used for qualitative and semi-quantitative gene
expression

CA 02666033 2009-05-15
2
analysis using cDNA as a starting template originating from a variety of
eukaryotic and
prokaryotic sources.
An instrument for performing thermal cycles in controlled manner on samples in
tubes
using heating and cooling an extended metal block is disclosed in EP 0 236
069. In addition,
various instruments for performing, detecting, and monitoring such methods are
known in
the art, e.g. the Roche Cobas TaqMari instrument as described in EP 0 953 837
and the
Roche Lightcycler 480 instrument.
In most of these instruments thermal cyclers are used having a thermal block
comprising
recesses where receptacles holding the PCR reaction mixtures can be inserted.
Raising and
lowering the temperature of the block in discrete, pre-programmed steps is
presently mainly
done using Peltier elements with active heating and cooling. A Peltier element
is a solid-
state active heat pump which transfers heat from one side of the device to the
other side
against the temperature gradient under consumption of electrical energy.
Generally it is
made up from two tiles in between which conducting paths carrying quadrate p-
and n-
dotted semi-conductor cubes are placed. The application of continuous current
results in a
heat absorption on one side of the Peltier element resulting in a temperature
decrease on
this side, while on the other side heat is released resulting in a temperature
increase. Upon
reversal of the direction of the current flow also the direction of the heat
transport may be
changed. In addition thermal cyclers comprise a heat sink for absorbing and
dissipating heat
from another object using thermal contact.
In order to allow for an efficient heat transition the Peltier elements are
coupled to the
thermal block on one major surface and to the heat sink on the other major
surface on the
opposite side using high mechanical force. In order to compensate for the
unevenness of the
respective surfaces which are in physical contact resulting in a diminished
contact and an
increased heat transfer resistance thermal interface materials are used. Such
thermal
interface materials commonly are films made up from graphite as, e.g.,
disclosed in US
2006/0086118 or films additionally modified having diamante layers on both
major surfaces
as, e.g., disclosed in US 6 164 076.
However, as numerous thermal profiles are performed on such thermal cyclers
there is an
increased risk that the thermal interface materials may be harmed and degraded
or
displaced, e.g., by friction while thermal profiles are applied particularly
when the

CA 02666033 2009-05-15
3
dimensions of the Peltier element and the thermal block are very unequal
resulting in a
divers expansion of the Peltier element and the thermal block caused by the
heat applied.
An object of the present invention therefore is to provide a device for
heating and cooling
an object in a controlled manner permitting a good thermal contact between the
thermal
block and the Peltier element without the need for using a thermal interface
material.
Further features and embodiments will become apparent from the description and
the
accompanying drawings. It will be understood that the features mentioned above
and those
described hereinafter can be used not only in the combination specified, but
also in other
combinations or on their own, without departing from the scope of the present
disclosure.
Various implementations are schematically illustrated in the drawings and are
hereinafter
explained in detail with reference to the drawings. It is understood that both
the foregoing
general description and the following description of various embodiments are
exemplary
and explanatory only and are not meant to be restrictive or to be read into
the claims. The
accompanying drawings, which are incorporated in a constitutive part of this
specification,
illustrate some embodiments, and together with the description serve to
explain the
principles of the embodiments described herein.
Summary of the invention
A first subject of the invention is a device for heating and cooling an object
in a controlled
manner, said device comprising layered on top of another in the following
order from top
to bottom
- a thermal block (1),
- an element for heating and cooling (4), and
a heat sink (5),
characterized in that the surface of the thermal block facing the element for
heating and
cooling (1 a) and / or the surface of the element for heating and cooling
facing the thermal
block (4a) is covered with a solid film lubricant.

CA 02666033 2009-05-15
4
The second subject of the invention is an instrument for performing thermal
cycles at least
comprising a device for heating and cooling according to the invention.
The third subject of the invention is a method for conducting a thermal
profile comprising
- providing a receptacle on a thermal block of a device for heating and
cooling
according to the invention,
- providing a fluid to be heated and / or cooled in said receptacle,
- applying heat or cold to said fluid in said receptacle using said element
for heating
and cooling.
Brief description of the drawings
Preferred embodiments of the invention are described below, by way of example,
with
reference to the accompanying drawings, wherein:
Figure 1 shows a device for heating and cooling known in the art having a
thermal block
(1), an element for heating and cooling (4), and a heat sink (5), wherein a
film for heat
transfer is present between the thermal block and the element for heating and
cooling (2) as
well as between the element for heating and cooling and the heat sink (3).
Figure 2 displays a device for heating and cooling according to the invention
having a
thermal block (1), an element for heating and cooling (4), and a heat sink
(5), wherein the
surface of the thermal block facing the element for heating and cooling ( la)
(Fig. 2A), the
surface of the element for heating and cooling facing the thermal block (4a)
(Fig. 2B), or
both surfaces (la and 4a) (Fig. 2C) are covered with a solid film lubricant,
while the surface
of the element for heating and cooling facing the heat sink (4b) and the
surface of the heat
sink facing the element for heating and cooling (5a) are not covered with a
solid film
lubricant.
Figure 3 depicts a device for heating and cooling according to the invention
having a
thermal block (1), an element for heating and cooling (4), and a heat sink
(5), wherein the
surface of the thermal block facing the element for heating and cooling (1a)
and the surface

CA 02666033 2009-05-15
of the heat sink facing the element for heating and cooling (5a) (Fig. 3A),
the surface of the
element for heating and cooling facing the thermal block (4a) and the surface
of the heat
sink facing the element for heating and cooling (5a) (Fig. 3B), the surface of
the thermal
block facing the element for heating and cooling (la) and the surface of the
element for
5 heating and cooling facing the heat sink (4b) (Fig. 3C) or both major
surfaces of the
element for heating and cooling (4a and 4b) (Fig. 3D) are covered with a solid
film
lubricant.
Figure 4 shows a device for heating and cooling according to the invention
having a thermal
block (1), an element for heating and cooling (4), and a heat sink (5),
wherein all major
surfaces facing one another (la / 4a and 4b / 5a) (Fig. 4A) or both major
surfaces of one
interface and one major surface of the other interface (la, 4b / 5a; la / 4a,
5a; 4a, 4b / 5a; la
7 4a, 4b) (Fig. 4B-E) are covered with a solid film lubricant.
Figure 5 displays a device for heating and cooling according to the invention
having a
thermal block (1), an element for heating and cooling (4), and a heat sink
(5), wherein the
surface of the thermal block facing the element for heating and cooling (la)
(Fig. 5A), the
surface of the element for heating and cooling facing the thermal block (4a)
(Fig. 5B), or
both surfaces (la and 4a) (Fig. 5C) are covered with a solid film lubricant
and wherein a
film for heat transfer (3) is present between the element for heating and
cooling (4) and the
heat sink (5).
For sake of clarity the figures show gaps between the components which in
reality are
intended to not being present.
Detailed description of the invention
The present invention relates to a device for heating and cooling an object in
a controlled
manner and an instrument comprising such a device. The device comprises
layered on top
of another a thermal block, an element for heating and cooling, and a heat
sink. The
`thermal block' forms the part of a thermal cycler that is capable of
transferring heat to a
receptacle holding the reaction mixture. In certain embodiments the thermal
block
comprises recesses for holding tubes containing the reaction mixture. However,
a broad

CA 02666033 2009-05-15
6
variety of `receptacles' are known in the art comprising single tubes, tube
strips, particular
arrangements of single tubes in circular, linear or other geometric
alignments, capillaries as
well as multi-well plates (MWP) and are commonly made up from plastic
materials or glass.
The body of the thermal block of a thermal cycler is therefore typically
adapted to the
receptacle used in order to allow for a fast and efficient transition of
heating or cooling
energy. The thermal block is generally made up from a material having a high
heat
conductivity. Preferably the material is a metal, in certain embodiments it is
aluminum or
silver, wherein silver has an improved heat conductivity while aluminum is
more cost
effective.
The temperature of the thermal block is raised and lowered via discrete, pre-
programmed
steps using an `element for heating and cooling'. Such elements are well known
in the art.
An exemplary element for heating and cooling is a Peltier element. A Peltier
element
provides for a thermoelectric heating and cooling using the Peltier effect to
create a heat
flux between the junction of two different types of materials. Peltier
elements are small
solid-state devices that function as heat pumps. Typically a Peltier element
is a few
millimeters thick by a few millimeters to a few centimeters square. It is a
sandwich formed
by two ceramic plates with an array of small Bismuth Telluride cubes in
between. When a
direct current is applied heat is transported from one side of the device to
the other. The
cold side is commonly used to cool an electronic device. If the current is
reversed the device
makes an excellent heater.
The heat is removed on one side via a`heat sink'. Heat sinks function by
efficiently
transferring thermal energy from an object at high temperature to a second
object at a lower
temperature with a much greater heat capacity. This rapid transfer of thermal
energy
quickly brings the first object into thermal equilibrium with the second,
lowering the
temperature of the first object, fulfilling the heat sink's role as a cooling
device. Efficient
function of a heat sink relies on rapid transfer of thermal energy from the
first object to the
heat sink. The most common design of a heat sink is a metal device with many
fins. The
high thermal conductivity of the metal combined with its large surface area
result in the
rapid transfer of thermal energy to the surrounding. In addition a fan may be
used for
additionally cooling the heat sink. Other embodiments of a heat sink comprise
heat pipes
usually in combination with a heat exchanging surface such as metal fins and a
fan.

CA 02666033 2009-05-15
7
In order to allow for an efficient heat transfer from Peltier element to
thermal block and / or
the heat sink `thermal interface materials' are used in the art. Such thermal
interface
materials may be applied as films, greases, epoxies, and pads and are selected
in respect to
their thermal and electrical conductivity, operating temperature range and
expansion
coefficient. It is used to fill the gaps between thermal transfer surfaces,
such as between
Peltier element and heat sink as well as between Peltier element and thermal
block, in order
to increase thermal transfer efficiency. These gaps are normally filled with
air which is a very
poor thermal conductor. Thermal interface materials are most commonly provided
as
white-colored paste or thermal grease, typically silicone oil filled with
aluminum oxide, zinc
oxide, boron nitride, pulverized silver, pulverized gold or beryllium oxide.
Furthermore,
paraffin/aluminum pads, boron nitride silicone sheets, graphite pads, adhesive
polymer
sheets, and silicone/fiberglass pads are used in the art.
Such a device for heating and cooling known in the art usable in a thermal
cycler is depicted
in Fig. 1 containing a thermal block (1), an element for heating and cooling
(4), and a heat
sink (5) additionally comprising a fan (6) for cooling the heat sink (5),
wherein a film for
heat transfer is present between the thermal block and the element for heating
and cooling
(2) as well as between the element for heating and cooling and the heat sink
(3). In order to
allow for an efficient heat transfer the elements making up the device are
connected to
another under mechanical force.
A particular problem of such devices for heating and cooling known in the art
is that
numerous thermal profiles are performed on such cyclers and that the thermal
block (1)
and the film for heat transfer (2) possess a diverse heat expansion
coefficient. The heat
expansion coefficient a for a thermal block made up from aluminum is known to
be
approximately 23x10-6/K while the heat expansion coefficient a for the ceramic
plates of a
Peltier element comprising aluminum oxide is approximately 6x10-6/K. This
results in a
vastly diverse expansion of the thermal block and the Peltier element each
time heat is
applied and thereby high shearing forces act on the film and the Peltier
element itself. Thus,
there is a high risk that these shearing forces may result in a disruption and
disintegration
or displacement of the film and thereby in an uneven heat transfer.
Furthermore, if the film
is made up from graphite which is capable of conducting electrical current
also electrical
malfunctions may occur. This problem becomes particularly apparent for large
thermal
blocks requiring the presence of more than one element for heating and cooling
in order to

CA 02666033 2009-05-15
8
provide for a homogenous temperature distribution across the thermal block. In
such an
embodiment a relative high difference of thermal expansion occurs between the
Peltier
element and the thermal block which may cause damage to the Peltier element if
the
shearing forces exceed the stability of the Peltier elements. A reduction of
the shearing
forces may be obtained by reduction of the force pressing the thermal block
onto the Peltier
elements or by using a thermal interface material with low friction.
In a device for heating and cooling according to the invention this problem is
solved by
omitting the film for heat transfer made up from thermal interface materials
and by coating
at least the surface of the thermal block facing the element for heating and
cooling and / or
the surface of the element for heating and cooling facing the thermal block
with a solid film
lubricant. By coating at least one of the surfaces that are brought into
physical contact when
the device for heating and cooling is assembled with a solid film lubricant
the friction forces
arising between the thermal block and the element for heating and cooling are
drastically
reduced. Thus, the risk for destruction of the element for heating and cooling
and / or the
surface of the thermal block is highly reduced.
Herein, the term `solid film lubricant' is used for materials that are applied
either from the
gas phase or from the liquid phase at approximately ambient temperature to a
maximum
temperature of 130 C onto a surface and which are characterized by a low
friction
coefficient. Furthermore, such solid film lubricants contain or consist of
organic
compounds, wherein the organic compounds may serve as adhering partners to the
base
material and / or serve as structural matrix and / or serve as the low
friction partner. Such
polymers are made up from poly-tetrafluoroethene or poly-tetrafluoroethylene
(PTFE),
polyimide, parylene F, fluorinated ethylene propylene (FEP) or other fluor
containing
polymers or any mixture thereof. The solid film lubricant may be homogeneous
or may
contain organic or inorganic lubricant particles such as graphite, graphite-
fluoride and / or
molybdenum compounds such as MoSz. However, coatings with an inorganic matrix
such
as nickel poly-tetrafluoroethylene (Ni-PTFE) are not considered to be solid
film lubricants
within the scope of this invention. Solid film lubricants may be hard or soft.
A solid film
lubricant is called hard when the solid film lubricant is applied on a glass
substrate and a
pencil with a hardness of 4H will not give a distinct indention if scratched
over the surface.
Examples for hard solid film lubricants are diamond like carbon (DLC) or micro
crystalline
diamond films, which are applied from the gas phase or the sol-gel coating SC
95 (Surface

CA 02666033 2009-05-15
9
Contacts GmbH Saarbrucken, Germany). Soft solid film lubricants are for
example
paryleneF films, applied from the gas phase or the PTFE containing coating SC
11 (Surface
Contacts GmbH Saarbrucken, Germany).
The coating with the solid film lubricant exhibits a low thickness of 0.2-25
m compared to
approximately 150 m thickness of a typical thermal interface material made of
graphite
and thereby the heat transmission is only minimally affected. It could even be
shown that
the heat transmission resistance of a coating with the solid film lubricant is
clearly reduced
when compared to the heat transmission resistance of a film for heat transfer
made up from
graphite. Thus, the device according to the invention besides reducing the
risk for an
electronic or thermal malfunction is also advantageous regarding a fast heat
transfer from
the element for heating and cooling to the thermal block and vice versa as
well as from the
element for heating and cooling to the heat sink and vice versa.
In particular embodiments it was found advantageous to use a soft solid film
lubricant on
the softer surface or a hard solid film lubricant on the harder surface. If
the element for
heating and cooling is a Peltier element then the solid film lubricant on the
ceramic plate of
the Peltier element preferably is a hard solid film lubricant. Usually the
thermal block is
made from aluminum or silver and constitutes the less hard substrate.
Therefore, preferably
a soft solid film lubricant is used when coating the thermal block surface
facing the element
for heating and cooling. Using a hard solid film lubricant as for example DLC
on a soft
surface such as aluminum is also feasible but may to some extend bear the risk
of damage to
the solid film which than may compromise the intended friction reduction.
In certain embodiments it is sufficient to use a solid film lubricant coating
only on the
surface of the thermal block, particularly on the surface facing the element
for heating and
cooling (la) as shown in Fig. 2A. Such embodiments are advantageous as
frictional
resistance between the thermal block and the element for heating and cooling
are reduced,
while the element for heating and cooling may remain uncoated. Preferably the
complete
thermal block is coated with a soft solid film lubricant in addition leading
to an improved
removability of the reaction vessels from the thermal block.
In another embodiment a solid film lubricant coating is applied only on the
surface of the
element for heating and cooling facing the thermal block (4a) as shown in Fig.
2B. This
embodiment is advantageous due to the relative small volume of the element for
heating

CA 02666033 2009-05-15
and cooling compared to the volumes of the thermal block, which allows
comparably
simple mass production at the coating step.
In yet another embodiment a solid film lubricant coating is applied on the
surface of the
thermal block facing the element for heating and cooling ( la) as well as on
the surface of the
5 element for heating and cooling facing the thermal block (4a) as shown in
Fig. 2C. In such
an embodiment both interacting surfaces contribute to the reduction of the
friction.
In the embodiments shown in Fig. 2 no solid film lubricant is coated on the
surface of the
element for heating and cooling facing the heat sink nor on the surface of the
heat sink
facing the element for heating and cooling. Beyond that no thermal interface
material is
10 placed between the element for heating and cooling and the heat sink. This
is feasible if the
relevant surfaces are very precisely flat and smooth and if there is excess
cooling power so
that there develops only marginal temperature differences between the two
surfaces. In
order to obtain more robust embodiments it is preferred to apply solid film
lubricant on
one or both of the relevant surfaces of the element for heating and cooling
and the heat sink
facing another as shown in Fig. 3 A-D and 4 A-D or to place a thermal
interface material in
between the surface of the element for heating and cooling and the heat sink
facing another
as shown in Fig. 5 A-C.
In particular embodiments both surfaces in physical contact with another when
the device
is assembled are coated with different solid film lubricants. For example the
surface of the
thermal block facing the element for heating and cooling may be coated with a
soft layer of
a solid film lubricant (e.g., a coating based on poly-tetrafluoroethene or
poly-
tetrafluoroethylene (PTFE)) and the surface of the element for heating and
cooling facing
the thermal block may be coated with a hard layer of a the solid film
lubricant (e.g., a
diamond-like carbon (DLC)).
In other embodiments both surfaces in physical contact with another when the
device is
assembled are coated with identical solid film lubricants. For example the
surface of the
thermal block facing the element for heating and cooling and the surface of
the element for
heating and cooling facing the thermal block may both be coated with a soft
layer of a the
solid film lubricant (e.g., a coating based on poly-tetrafluoroethene or poly-
tetrafluoroethylene (PTFE)) or may both be coated with a hard layer of a the
solid film
lubricant (e.g., a diamond-like carbon (DLC)), respectively.

...... . .. ...:. . ..... ..,,. .... . . .,.... , . . , ... _ :...,., , .
..... ..... .. ... . , , .... , ..:.,. . ....., . ... .. . ... . .. . ...... .
.
CA 02666033 2009-05-15
11
These embodiments are advantageous as the coated elements for heating and
cooling
exhibit an improved durability due to reduced frictional resistance.
Furthermore, the
coating of the major surfaces of the element for heating and cooling can be
performed by
methods very well known in the art.
An instrument for performing thermal cycles commonly comprises a thermal block
having
a top surface and a plurality of recesses communicating with said top surface
for holding
plastic reaction vessels wherein reaction mixtures can be contained. The
footprint of the
thermal block is in the range of some cm in square. In particular embodiments
the footprint
is suitable for a plurality of vessels in the format of a multi-well plate.
The opening of each
vessel is closed, preferably with a transparent closure that allows
examination of the vessel
content e.g. by measuring the light emission emitted by fluorescent dyes. A
frame with
corresponding apertures is placed above the plurality of vessels and pressed
towards the
thermal block, causing intimate contact of the plastic vessels with the
surface of the recesses
in the thermal block. In preferred embodiments the frame is heated in order to
heat the
closures and avoid condensation of liquid at the closures.
The thermal block is stacked on top of an element for heating and cooling and
a heat sink as
schematically shown in Fig. 2-5. Fixture means e.g. spring loaded screws are
used to press
the stack together.
A fluid is brought into contact with a heat exchanging surface of the heat
sink in to order to
transport away the excess heat. Preferably the fluid is air and at least one
fan blows air over
the fins of the heat sink.
Sensors in the thermal block measure the temperature of the thermal block and
a
programmable electronic unit controls the heating and cooling of the heating
and cooling
element in order to perform a temperature profile within the reaction mixture
in the
reaction vessels.
For monitoring the progress of a reaction in the reaction vessels a preferred
embodiment of
an instrument comprises a continuous or semi-continuous working detection
system and a
data processing unit comprising an entry unit, a display unit, a storage unit
and auxiliary
units which are state of the art to handle, store, retrieve and display the
detection data

CA 02666033 2009-05-15
12
together with other process data in a usable form. A preferred form of the
detection system
is fluorescence detection which is well known in the art.
The instrument according to the invention comprises a device for heating and
cooling as
described above, wherein at least one of the surfaces of the thermal block and
/ or the
element for heating and cooling are coated with a solid film lubricant. The
device for
heating and cooling is positioned within the instrument in such a manner to
permit a
defined and predetermined physical interaction with a receptacle, when said
receptacle is
inserted into the instrument and brought into contact with said device. In
certain
embodiments the instrument comprises a heat control. In addition an instrument
according to the invention may further comprise a housing, a power supply,
supply and
disposal means for other media as cooling air and/or pressurized air and/or
cooling water
and/or vacuum, auxiliary means for handling reaction vessels and for control
and
maintenance.
The device for heating and cooling as described above may also be used in a
method for
conducting a thermal profile comprising, wherein a receptacle is provided on a
thermal
block of a device for heating and cooling according to the invention, a fluid
to be heated
and / or cooled is provided in said receptacle, and heat or cold is applied to
said fluid in said
receptacle using said element for heating and cooling. The thermal profile may
contain
repeated thermocycles, which in certain aspects are suitable for performing a
polymerase
chain reaction and wherein the fluid to be heated is a reaction mixture for
performing a
polymerase chain reaction containing a nucleic acid sample to be amplified.
Examples
Example 1
Application of a hard solid film lubricant on a thermal block
The rear side of a thermal block made up from aluminum enabling the physical
contact
with the Peltier element was coated under vacuum conditions with a Diamond-
like carbon
(DLC) to form a layer having a thickness of 0.5 m, while the temperature of
the thermal
block was approximately 130 C.

. z.,. ,.._ . .... ,.._.:. . _.. . ....... ,. ...
CA 02666033 2009-05-15
13
Example 2
Application of a hard solid film lubricant on a device for heating and cooling
In analogy to Example 1 the surface of a Peltier element (Marlow Industries,
Inc. Dallas,
TX, USA) was coated under vacuum conditions with a Diamond-like carbon (DLC)
to
form a layer having a thickness of 0.5 m, while the temperature of the
Peltier element was
not raised above 125 C.
Example 3
Application of a hard solid film lubricant on a thermal block
The rear side of a thermal block made up from aluminum enabling the physical
contact
with the Peltier element was coated with the sol-gel hard coating SC 95
(Surface Contacts
GmbH Saarbrucken, Germany) using a spray coating method known in the art to
form a
layer having a thickness of 6 m. After the application the coating on the
thermal block was
stoved for 0.5 h at 125 C.
Example 4
Application of a hard solid film lubricant on a device for heating and cooling
In analogy to Example 3 the surface of a Peltier element (Marlow Industries,
Inc. Dallas,
TX, USA) providing heat was coated with the sol-gel hard coating SC 95
(Surface Contacts
GmbH Saarbrucken, Germany) using a spray coating method known in the art to
form a
layer having a thickness of 6 m. After the application the coating on the
thermal block was
stoved for 0.5 h at 125 C.

CA 02666033 2009-05-15
14
Example 5
Application of a soft solid film lubricant on a thermal block
The rear side of a thermal block made up from aluminum enabling the physical
contact
with the Peltier element was coated with SC 11 (Surface Contacts GmbH
Saarbrucken,
Germany), a solid film lubricant containing poly-tetrafluoroethylene (PTFE),
using a spray
coating method known in the art to form a layer having a thickness of
approximately 16
m. After the application the coating was dried for 0.5 h at 280 C.
Example 6
Application of a soft solid film lubricant on device for heating and cooling
In analogy to Example 5 the surface of a Peltier element (Marlow Industries,
Inc. Dallas,
TX, USA) providing heat was coated with SC 11 (Surface Contacts GmbH
Saarbrucken,
Germany), a solid film lubricant containing poly-tetrafluoroethylene (PTFE),
using a spray
coating method known in the art to form a layer having a thickness of
approximately 16
m. After the application the coating was dried for 6 h at 125 C.
Example 7
Analysis of a device for heating and cooling known in the art
A device for heating and cooling comprising a thermal block for accepting
reaction vessels
in form of microtiter plates, six Peltier elements (Marlow Industries, Inc.
Dallas, TX, USA),
a film for heat transfer having a thickness of approximately 160 pm and being
made up
from graphite, and a heat sink was assembled in the described order using
screws providing
a surface compression of 700 N/cm2. In addition the thermal block was covered
with a
coating made up from Nickel poly-tetrafluoroethylene (Ni-PTFE) having a
thickness of
approximately 25 m. Using an electronic control the device for heating and
cooling was
subjected to repeated thermal cycles resembling typical PCR cycles. After
approximately
1000 cycles the film for heat transfer was displaced from its reference
position between the

CA 02666033 2009-05-15
thermal block and the Peltier element leading to a short-circuit in the power
supply of the
Peltier element.
Example 8
5 Analysis of a device for heating and cooling having no film for heat
transfer
An assembly as described in Example 7 was provided except that no film for
heat transfer
was incorporated. Using an electronic control the device for heating and
cooling was
subjected to repeated thermal cycles resembling typical PCR cycles. After less
than 1000
cycles the thermal block showed massive disintegration of the surface in
contact with the
10 Peltier element having depth up to approximately 0.5 mm.
Example 9
Assembly for a fast thermal cycle simulation
In order to allow for a fast examination of durability and lifespan of
elements for heating
15 and cooling a thermal block, a Peltier element, a graphite film thermal
interface material
and a heat sink were mounted on top of another in said order into a piling
under a tension
force of 700 N/cm2. In order to examine the impact of various measures to
improve the
lifespan of the element for heating and cooling the Peltier element was
mechanically moved
back and forth parallel to its major surfaces for 0.5 mm at a frequency of 2
Hz and a
constant temperature of 95 C. In this assembly, one movement back and forth
represents
the simulation of the relative movement of the Peltier element in relation to
the thermal
block caused by different heat expansion coefficients during one thermal cycle
of a PCR.

CA 02666033 2009-05-15
16
Example 10
Analysis of a device for heating and cooling having no film for heat transfer
using the
assembly for a fast thermal cycle simulation
The element for heating and cooling known in the art and as described in
Example 7 and 8
was subjected to the treatment in the assembly for fast thermal cycle
simulation as outlined
in Example 9. After less than 1000 cycles the thermal block showed massive
disintegration
of the surface in contact with the Peltier element having depth up to
approximately 0.5 mm
confirming the results outlined in Example 8.
Example 11
Analysis of a device for heating and cooling according to the invention using
the assembly
for a fast thermal cycle simulation
The device for heating and cooling as described in Example 5 was subjected to
the treatment
in the assembly for fast thermal cycle simulation as outlined in Example 9.
The surface of
the thermal block made up from aluminum facing the Peltier element and
enabling the
physical contact with the Peltier element was coated with SC 11 (Surface
Contacts GmbH
Saarbrucken, Germany). No film for heat transfer was present in between the
Peltier
element and the thermal block. After 102.000 cycles the interacting surfaces
were analyzed.
Except for a minor carry over of the solid film lubricant SC 11 from the
surface of the
thermal block facing the Peltier element to the surface of the Peltier element
facing the
thermal block no disintegration of the surfaces was detected. In additional
experiments the
results were reproduced and no disintegration of the surfaces was detected at
up to 200.000
cycles.
Similar results were obtained using a device for heating and cooling
comprising a thermal
block according to Example 1 or 3 as well as comprising a Peltier element
according to
Example 2, 4 or 6.

CA 02666033 2009-05-15
17
Example 12
Analysis of a device for heating and cooling according to the invention using
the assembly
for a fast thermal cycle simulation
The device for heating and cooling comprising a thermal block as described in
Example 5
and a Peltier element as described in Example 4 was subjected to the treatment
in the
assembly for fast thermal cycle simulation as outlined in Example 9. The
surface of the
thermal block made up from aluminum facing the Peltier element and enabling
the physical
contact with the Peltier element was coated with SC 11 (Surface Contacts GmbH
Saarbrucken, Germany), while the surface of the Peltier element facing the
thermal block
was coated with the sol-gel hard coating SC 95 (Surface Contacts GmbH
Saarbrucken,
Germany). No film for heat transfer was present in between the Peltier element
and the
thermal block. After 100.000 cycles the interacting surfaces were analyzed.
Except for a
minor carry over of the solid film lubricant SC 11 from the surface of the
thermal block
facing the Peltier element to the surface of the Peltier element facing the
thermal block no
disintegration of the surfaces was detected. Beyond that the frictional force
was further
decreased compared to the device for heating and cooling used in Example 11 as
the power
input of the actuator in the assembly was reduced, which is indicative for the
frictional force
present in the assembly.

CA 02666033 2009-05-15
18
Reference numerals
1 thermal block
la surface of the thermal block facing the element for heating and cooling
2 film for heat transfer
3 film for heat transfer
4 element for heating and cooling
4a surface of the element for heating and cooling facing the thermal block
4b surface of the element for heating and cooling facing the heat sink
heat sink
5a surface of the heat sink facing the element for heating and cooling
6 fan
7 circuit

Representative Drawing
A single figure which represents the drawing illustrating the invention.
Administrative Status

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Please note that "Inactive:" events refers to events no longer in use in our new back-office solution.

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Event History

Description Date
Time Limit for Reversal Expired 2015-05-15
Application Not Reinstated by Deadline 2015-05-15
Deemed Abandoned - Failure to Respond to Maintenance Fee Notice 2014-05-15
Inactive: Abandon-RFE+Late fee unpaid-Correspondence sent 2014-05-15
Application Published (Open to Public Inspection) 2009-11-19
Inactive: Cover page published 2009-11-18
Inactive: IPC assigned 2009-11-05
Inactive: First IPC assigned 2009-10-21
Inactive: IPC assigned 2009-10-21
Inactive: IPC assigned 2009-10-21
Inactive: IPC assigned 2009-10-21
Inactive: IPC assigned 2009-10-21
Application Received - Regular National 2009-06-09
Filing Requirements Determined Compliant 2009-06-09
Inactive: Filing certificate - No RFE (English) 2009-06-09

Abandonment History

Abandonment Date Reason Reinstatement Date
2014-05-15

Maintenance Fee

The last payment was received on 2013-04-24

Note : If the full payment has not been received on or before the date indicated, a further fee may be required which may be one of the following

  • the reinstatement fee;
  • the late payment fee; or
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Please refer to the CIPO Patent Fees web page to see all current fee amounts.

Fee History

Fee Type Anniversary Year Due Date Paid Date
Application fee - standard 2009-05-15
MF (application, 2nd anniv.) - standard 02 2011-05-16 2011-03-23
MF (application, 3rd anniv.) - standard 03 2012-05-15 2012-03-23
MF (application, 4th anniv.) - standard 04 2013-05-15 2013-04-24
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
F. HOFFMANN-LA ROCHE AG
Past Owners on Record
HERBERT HARTTIG
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Description 2009-05-15 18 827
Abstract 2009-05-15 1 10
Claims 2009-05-15 2 62
Drawings 2009-05-15 8 147
Representative drawing 2009-11-12 1 8
Cover Page 2009-11-12 1 34
Filing Certificate (English) 2009-06-09 1 157
Reminder of maintenance fee due 2011-01-18 1 112
Reminder - Request for Examination 2014-01-16 1 116
Courtesy - Abandonment Letter (Request for Examination) 2014-07-10 1 164
Courtesy - Abandonment Letter (Maintenance Fee) 2014-07-10 1 171